chr18-48853255-C-T

Variant names:

• chr18-48853255-C-T
• rs1317355
• NM_014772.3:c.1528-4333C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014772.3(CTIF):​c.1528-4333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 151,926 control chromosomes in the GnomAD database, including 5,732 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5732 hom., cov: 32)
• Consequence: CTIF NM_014772.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 2 publications found

Genes affected

CTIF (HGNC:23925): (cap binding complex dependent translation initiation factor) CTIF is a component of the CBP80 (NCBP1; MIM 600469)/CBP20 (NCBP2; MIM 605133) translation initiation complex that binds cotranscriptionally to the cap end of nascent mRNA. The CBP80/CBP20 complex is involved in a simultaneous editing and translation step that recognizes premature termination codons (PTCs) in mRNAs and directs PTC-containing mRNAs toward nonsense-mediated decay (NMD). On mRNAs without PTCs, the CBP80/CBP20 complex is replaced with cytoplasmic mRNA cap-binding proteins, including EIF4G (MIM 600495), and steady-state translation of the mRNAs resumes in the cytoplasm (Kim et al., 2009 [PubMed 19648179]).[supplied by OMIM, Dec 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTIF	NM_014772.3	c.1528-4333C>T		intron_variant	Intron 10 of 11	ENST00000256413.8	NP_055587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTIF	ENST00000256413.8	c.1528-4333C>T		intron_variant	Intron 10 of 11	1	NM_014772.3	ENSP00000256413.3
CTIF	ENST00000382998.8	c.1534-4333C>T		intron_variant	Intron 11 of 12	1		ENSP00000372459.3
CTIF	ENST00000587860.1	n.1665-4333C>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40570 AN: 151808 Hom.: 5721 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.267 AC: 40603 AN: 151926 Hom.: 5732 Cov.: 32 AF XY: 0.265 AC XY: 19642 AN XY: 74240

African (AFR) AF: 0.334 AC: 13837 AN: 41416

American (AMR) AF: 0.330 AC: 5028 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1239 AN: 3468

East Asian (EAS) AF: 0.176 AC: 909 AN: 5166

South Asian (SAS) AF: 0.125 AC: 600 AN: 4810

European-Finnish (FIN) AF: 0.192 AC: 2026 AN: 10530

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16148 AN: 67966

Other (OTH) AF: 0.275 AC: 580 AN: 2106

Alfa AF: 0.254 Hom.: 7763

Bravo AF: 0.285

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.48
DANN	Benign	0.49
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1317355; hg19: chr18-46379626;